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Monthly Archives for October 2012

This year’s Nobel Prize in Chemistry goes to Robert Lefkowitz and Brian Kobilka for their study of how cells interact with their environment. Everyone has heard of various “receptors.” The term has pretty well entered the common lexicon, and much of that is because a large quantity of modern drugs interact with these receptors, called G-protein coupled receptors.

What’s exciting about this work is not that it is a story of how science evolves and deepens over the years, even though it is: from the late 60’s when Lefkowitz enters the picture, through the discovery of the G-proteins (which itself earned Gilman and Rodbell the 1994 Nobel Prize in Physiology or Medicine,) through Kobilka’s discovery of the gene that encodes for a particular receptor of interest – the beta-adrenergic receptor. Any of you who are taking beta-blockers for hypertension are tinkering with the function of this receptor on a daily basis. This long-running line of research recently culminated in Kobilka’s recent publication (Nature469, 175) of the crystal structure of an activated beta-adrenergic receptor. As the Nobel committee so eloquently put it , this was “a molecular masterpiece – the result of decades of research.”

Rather, what is exciting was Kobilka’s observation that the structure of this beta receptor was substantially similar to the rhodopsin detector in the eye. The implication of Kobilka’s work was that the body was able to use similar structures to accomplish widely different tasks and that at least our ability to see shares a common evolutionary root with other wholly internal sensing mechanisms. It has undoubtedly had and will continue to have a great deal of impact on our search for new pharmaceutical therapies but also on our understanding of the complex biomolecular machinery of life.

As amazing as this work is, I can’t help but feel a bit conflicted about this Nobel Prize. Understand that this has nothing to do with the research or the researchers, but rather is about the choices of the Nobel committee. This award feels like an underhanded way of awarding a second Nobel Prize in Physiology. This may be unfair on two counts. First, there is a long track record of biochemistry receiving well-deserved chemistry prizes for chemical research. The classic example of this was Frederick Sanger, who won the 1958 Nobel Prize in Chemistry for the structure of proteins, particularly insulin, and then shared the 1980 prize for his work on nucleic acid. The work, while on biological substrates, was clearly well ensconced in the fields of chemical research. Second, it is undeniable that certain frontiers of science are in the realm of biological systems and that the research that is timely and novel right now will inevitably have some biological bent. What bothers me is that the motivation of the decades of research was not in my mind the chemistry underlying the receptor, but rather the physiology of the receptor’s behavior and its mechanism of action. Further, the capstone piece of work cited by the Nobel committee was the Nature paper mentioned earlier which dealt with the structure of an activated receptor, which calls Watson and Crick’s 1962 Nobel Prize to mind. It is of note that this work received the Nobel Prize in Physiology or Medicine.

Many chemists struggle with the “bio-creep” of the prizes, which is probably inevitable and a little healthy. I will also admit to have given a little friendly joshing to some of my colleagues who have complained about it. But in this particular case, I share the sentiments expressed at Chembark that this was excellent work deserving of the Nobel Prize in Physiology or Medicine.

This year’s Nobel Prize in Physics was awarded to Serge Haroche and David Wineland for their work in the experimental measurement of quantum systems. The official announcement might make the area of their work seem rather vague and a cursory glance at the two laureate’s work could lead someone to believe that this award was for work in a similar, but somewhat unrelated area. This is most certainly not the case. The work of Haroche and Wineland has enabled experimental investigation of quantum computing. The field of quantum computing was itself postulated in 1982 by another Nobel physics laureate, Richard Feynman, and has the potential to change the way we think about computing and the processing of information.

Dr. Haroche’s groundbreaking work, published in 1996, showed experimentally that quantum systems “leaked” information to their environment, which was heralded as the explanation for wavefunction collapse, and the implications for that decoherence on the measurement of the quantum state. To simplify it, think back to the classic gedaken experiment about Schrodinger’s cat. In this experiment, the animal’s survival is predicated on the decay of a single atom, which is a quantum event. We then say that the animal must be in a superposition of the two states labelled “alive” and “dead.” Quantum decoherence is the process by which the observed wave function collapses into a classical state, or in the cat-model, how the system falls back into the cat being either alive or dead. Haroche’s key paper (Phys. Rev. Lett.77, 4887) provided key insight into this process of measurement and posited that quantum decoherence is the boundary between classical and quantum behavior that is reached when the quantum system interacts with its environment.

Dr. Wineland, both a Rabi Award and National Medal of Science winner, used quantum systems of trapped ions to perform computations, pulling together and building on the Nobel prize winning work of Wolfgang Paul (ion trapping, 1989), Steven Chu, Claude Cohen-Tannoudji, and William Phillips (laser cooling of atoms, 1997) and Haroche’s work to show that entangled quantum systems could be made to process information and then that the processed information could be retrieved reliably. While quantum computing is in a relative infancy, Wineland’s early work in the area also enabled more precise atomic clocks and made the global positioning system possible.

The first announcement of this year’s Nobel season was made this morning. The Nobel Prize for Physiology or Medicine has gone to John Gurdon and Shinya Yamanaka. This is a case where the work being awarded is very well known, even outside of scientific circles. Induced pluripotent stem cells, colloquially known as “adult stem cells,” have been discussed in many forums for their potential for revolutionary medical treatments.

What’s exciting about this work is that this discovery is key to enabling future therapeutic successes of stem cells. One such therapeutic application is one that I have long considered to be a Holy Grail problem: the growth of complex organs for transplants. Currently, there have been some early successes in this area, particularly in growing relatively simple organs such as bladders (first performed in 2006) and tracheae (first clinical use in 2008,) we are quite far away from organs such as livers, hearts, and kidneys. Both of these tissue engineering successes have used a type of stem cell that can be isolated from a patients own bone marrow, rather than the induced pluripotent cells that have won this year’s Nobel. It is expected that Yamanaka’s work will be key to developing more complex organs.

From the Nobel perspective, this work should have been on anyone’s short list of potential winners. Yamanaka shared last year’s Wolf Prize in Medicine with Rudolf Jaenisch of MIT for this discovery and Jaenisch’s subsequent use of the technique to treat a genetic disease in a mammal, thus providing a proof of concept for its therapeutic use. What is interesting is that the Nobel committee did not choose to include Jaenisch in today’s award.

Induced pluripotent stem cells have a long history. Gurdon’s work in replacing the nuclear material of a frog egg cell with the nuclear material from a tadpole was originally performed in 1962. While this success would not appear to deal with stem cells, the learning that a mature, differentiated cell could be reverted to an immature state was key to Yamanaka’s later work. What Yamanaka did was to find the specific gene sequences necessary to revert a mature cell to a stem cell, and then transfecting adult cells in order to force the expression of those sequences.

Inveterate geeks will recall the scene in Star Trek 4 where Dr. McCoy gives a dialysis patient a pill that induces the growth of a new kidney. Induced pluripotent stem cells may bring us closer to those kinds of therapies are available outside of the movie theater.

Dr. Chudnovsky is a professor of operations research and mathematics at Columbia University and studies graph theory. I’ve seen a lot of very interesting papers in the past few years where the specific tractability of analysis that you get with graphs has been used to elucidate phenomena from failovers on communications networks to growth dynamics in social media. Dr. Chudnovsky’s work is fundamental in connecting the specifics of graph theory to other branches of analysis.

Dr. Mazmanian is a professor of biology at CalTech. Regular readers of this blog and my Google+ stream will understand why I’m excited about this guy. His area of study is the interaction between host organisms and their beneficial microbial symbiotes. This area of research and the underlying premise that at least in humans, we can treat our bodies as an ecosystem rather than an organism promises to shape medical research outcomes for the next half-century.

I’m grateful to Ed Darrell for breaking the news when I was sound asleep!